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Erik De Schutter

Publications and source records attributed to Erik De Schutter.

At least 19 recordsLinked to original sources
PubMed2006

Anomalous diffusion in Purkinje cell dendrites caused by spines.

We combined local photolysis of caged compounds with fluorescence imaging to visualize molecular diffusion within dendrites of cerebellar Purkinje cells. Diffusion of a volume marker, fluorescein dextran, within spiny dendrites was remarkably slow in comparison to its diffusion in smooth dendrites. Computer simulations indicate that this retardation is due to a transient trapping of molecules within dendritic spines, yielding anomalous diffusion. We considered the influence of spine trapping on the diffusion of calcium ions (Ca(2+)) and inositol-1,4,5-triphospate (IP(3)), two synaptic second messengers. Diffusion of IP(3) was strongly influenced by the presence of dendritic spines, while Ca(2+) was removed so rapidly that it could not diffuse far enough to be trapped. We conclude that an important function of dendritic spines may be to trap chemical signals and thereby create slowed anomalous diffusion within dendrites.

Animals↗
PubMed2006

Dynamic synchronization of Purkinje cell simple spikes.

Purkinje cells (PCs) integrate all computations performed in the cerebellar cortex to inhibit neurons in the deep cerebellar nuclei (DCN). Simple spikes recorded in vivo from pairs of PCs separated by <100 microm are known to be synchronized with a sharp peak riding on a broad peak, but the significance of this finding is unclear. We show that the sharp peak consists exclusively of simple spikes associated with pauses in firing. The broader, less precise peak was caused by firing-rate co-modulation of faster firing spikes. About 13% of all pauses were synchronized, and these pauses had a median duration of 20 ms. As in vitro studies have reported that synchronous pauses can reliably trigger spikes in DCN neurons, we suggest that the subgroup of spikes causing the sharp peak is important for precise temporal coding in the cerebellum.

Animals↗
PubMed2006

Complex parameter landscape for a complex neuron model.

The electrical activity of a neuron is strongly dependent on the ionic channels present in its membrane. Modifying the maximal conductances from these channels can have a dramatic impact on neuron behavior. But the effect of such modifications can also be cancelled out by compensatory mechanisms among different channels. We used an evolution strategy with a fitness function based on phase-plane analysis to obtain 20 very different computational models of the cerebellar Purkinje cell. All these models produced very similar outputs to current injections, including tiny details of the complex firing pattern. These models were not completely isolated in the parameter space, but neither did they belong to a large continuum of good models that would exist if weak compensations between channels were sufficient. The parameter landscape of good models can best be described as a set of loosely connected hyperplanes. Our method is efficient in finding good models in this complex landscape. Unraveling the landscape is an important step towards the understanding of functional homeostasis of neurons.

Algorithms↗
PubMed2006

A novel high channel-count system for acute multisite neuronal recordings.

Multisite recording represents a suitable condition to study microphysiology and network interactions in the central nervous system and, therefore, to understand brain functions. Several different materials and array configurations have been proposed for the development of new probes utilized to record brain activity from experimental animal models. We describe new multisite silicon probes that broaden the currently available application base for neuroscientists. The array arrangement of the probes recording sites was extended to increase their spatial resolution. Probes were integrated with a newly developed electronic hardware and novel software for advanced real-time processing and analysis. The new system, based on 32- and 64-electrode silicon probes, proved very valuable to record field potentials and single unit activity from the olfactory-limbic cortex of the in vitro isolated guinea-pig brain preparation and to acutely record unit activity at multiple sites from the cerebellar cortex in vivo. The potential advantages of the new system in comparison to the currently available technology are discussed.

Action Potentials↗
PubMed2006

Dendritic amplification of inhibitory postsynaptic potentials in a model Purkinje cell.

In neurons with large dendritic arbors, the postsynaptic potentials interact in a complex manner with active and passive membrane properties, causing not easily predictable transformations during the propagation from synapse to soma. Previous theoretical and experimental studies in both cerebellar Purkinje cells and neocortical pyramidal neurons have shown that voltage-dependent ion channels change the amplitude and time-course of postsynaptic potentials. We investigated the mechanisms involved in the propagation of inhibitory postsynaptic potentials (IPSPs) along active dendrites in a model of the Purkinje cell. The amplitude and time-course of IPSPs recorded at the soma were dependent on the synaptic distance from the soma, as predicted by passive cable theory. We show that the effect of distance on the amplitude and width of the IPSP was significantly reduced by the dendritic ion channels, whereas the rise time was not affected. Somatic IPSPs evoked by the activation of the most distal synapses were up to six times amplified owing to the presence of voltage-gated channels and the IPSP width became independent of the covered distance. A transient deactivation of the Ca(2+) channels and the Ca(2+)-dependent K(+) channels, triggered by the hyperpolarization following activation of the inhibitory synapse, was found to be responsible for these dynamics. Nevertheless, the position of activated synapses had a marked effect on the Purkinje cell firing pattern, making stellate cells and basket cells most suitable for controlling the firing rate and spike timing, respectively, of their target Purkinje cells.

Animals↗
PubMed2006

Topographical organization of pathways from somatosensory cortex through the pontine nuclei to tactile regions of the rat cerebellar hemispheres.

The granule cell layer of the cerebellar hemispheres contains a patchy and noncontinuous map of the body surface, consisting of a complex mosaic of multiple perioral tactile representations. Previous physiological studies have shown that cerebrocerebellar mossy fibre projections, conveyed through the pontine nuclei, are mapped in registration with peripheral tactile projections to the cerebellum. In contrast to the fractured cerebellar map, the primary somatosensory cortex (SI) is somatotopically organized. To understand better the map transformation occurring in cerebrocerebellar pathways, we injected axonal tracers in electrophysiologically defined locations in Sprague-Dawley rat folium crus IIa, and mapped the distribution of retrogradely labelled neurons within the pontine nuclei using three-dimensional (3-D) reconstructions. Tracer injections within the large central upper lip patch in crus IIa-labelled neurons located centrally in the pontine nuclei, primarily contralateral to the injected side. Larger injections (covering multiple crus IIa perioral representations) resulted in labelling extending only slightly beyond this region, with a higher density and more ipsilaterally labelled neurons. Combined axonal tracer injections in upper lip representations in SI and crus IIa, revealed a close spatial correspondence between the cerebropontine terminal fields and the crus IIa projecting neurons. Finally, comparisons with previously published three-dimensional distributions of pontine neurons labelled following tracer injections in face receiving regions in the paramedian lobule (downloaded from http://www.rbwb.org) revealed similar correspondence. The present data support the coherent topographical organization of cerebro-ponto-cerebellar networks previously suggested from physiological studies. We discuss the present findings in the context of transformations from cerebral somatotopic to cerebellar fractured tactile representations.

Animals↗
PubMed2005

Temporal characteristics of tactile stimuli influence the response profile of cerebellar Golgi cells.

An increasing number of studies have investigated the effect of stimulation parameters on neuronal response properties. Here, we describe the effect of temporal characteristics of tactile stimuli, more specifically the stimulation frequency and duration, on the response profile of simultaneously recorded cerebellar and cerebral cortical units in ketamine-xylazine anaesthetized rats. Long stimulus durations (>50 ms) elicited ON and OFF excitatory components in response to the stimulus onset and offset respectively, in both the cortex and the cerebellum. Golgi cells responded on average 7.5 ms later to the stimulus withdrawal than to the stimulus onset. Furthermore, the corticopontine OFF responses in the cerebellum and OFF responses in the cortex showed congruent latency decreases and amplitude increases for longer stimulus durations (50-200 ms). Decreasing the stimulus frequency similarly affected the latency and amplitude of the responses for inter-stimuli intervals shorter than 200 ms. In view of these results, we speculate that the stimulus offset is regarded as a novel input, because both paradigms resulted in similar response amplitude and latency modifications. Finally, the results suggest that a 100-200 ms time window can be of particular importance for cerebellar processing of information in the somatosensory system.

Action Potentials↗
PubMed2005

Biophysically detailed modelling of microcircuits and beyond.

Realistic bottom-up modelling has been seminal to understanding which properties of microcircuits control their dynamic behaviour, such as the locomotor rhythms generated by central pattern generators. In this article of the TINS Microcircuits Special Feature, we review recent modelling work on the leech-heartbeat and lamprey-swimming pattern generators as examples. Top-down mathematical modelling also has an important role in analyzing microcircuit properties but it has not always been easy to reconcile results from the two modelling approaches. Most realistic microcircuit models are relatively simple and need to be made more detailed to represent complex processes more accurately. We review methods to add neuromechanical feedback, biochemical pathways or full dendritic morphologies to microcircuit models. Finally, we consider the advantages and challenges of full-scale simulation of networks of microcircuits.

Animals↗
PubMed2005

Microcircuits in action--from CPGs to neocortex.

To understand the interface between global brain function and molecular neuroscience--that is, the microcircuit level--a major challenge. Such understanding is prerequisite if we are to account for neural function in cellular terms. Very few vertebrate microcircuits are yet understood because their analysis is demanding technically. In this review of the TINS Microcircuits Special Feature, we attempt to shed light on the problem by comparing the operation of four types of microcircuit, to identify common molecular and cellular components. Central pattern generator (CPG) networks underlying rhythmic movements and hippocampal microcircuits that generate gamma and theta rhythms are compared with the neocortical microcircuits used in cognitive tasks and a cerebellar network. The long-term goal is to identify the components of a molecular and synaptic tool kit for the design of different microcircuits.

Animals↗
PubMed2005

Oscillations in the cerebellar cortex: a prediction of their frequency bands.

Local recurrent connections endow the cerebellar cortex with an intrinsic dynamics. We performed computer simulations to predict the frequency bands of the oscillations that will most likely emerge. Feedback inhibition from the Golgi to the granule cells induced 10-50 Hz oscillations, the period at resonance being approximately equal to four times the maximum conduction delay generated along the parallel-fiber connections from granule to Golgi cells. In the molecular layer, the interneurons tended to induce fast oscillations (100-250 Hz), having a period equal to about four times the delay over their reciprocal synaptic connections. Finally, although the presence of lateral inhibition among the Purkinje cells has not been firmly established, reciprocal Purkinje-cell synapses are predicted to transform the cerebellar cortex into a potential temporal integrator.

Animals↗
PubMed2005

The effect of NMDA receptors on gain modulation.

The ability of individual neurons to modulate the gain of their input-output function is important for information processing in the brain. In a recent study, shunting inhibition was found to modulate the gain of cerebellar granule cells subjected to simulated currents through AMPA receptor synapses. Here we investigate the effect on gain modulation resulting from adding the currents mediated by NMDA receptors to a compartmental model of the granule cell. With only AMPA receptors, the changes in gain induced by shunting inhibition decreased gradually with the average firing rate of the afferent mossy fibers. With NMDA receptors present, this decrease was more rapid, therefore narrowing the bandwidth of mossy fiber firing rates available for gain modulation. The deterioration of gain modulation was accompanied by a reduced variability of the input current and saturation of NMDA receptors. However, when the output of the granule cell was plotted as a function of the average input current instead of the input firing frequency, both models showed very similar response curves and comparable gain modulation. We conclude that NMDA receptors do not directly impair gain control by shunting inhibition, but the effective bandwidth decreases as a consequence of the increased total charge transfer.

Animals↗
PubMed2004

Color discrimination involves ventral and dorsal stream visual areas.

We used positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) in human subjects to investigate whether the ventral and dorsal visual stream cooperate when active judgements about color have to be made. Color was used as the attribute, because it is processed primarily in the ventral stream. The centrally positioned stimuli were equiluminant shades of brown. The successive color discrimination task was contrasted to a dimming detection task, in which retinal input was identical but with double the number of motor responses. The stimulus presentation rate was parametrically varied and a constant performance level was obtained for all conditions. The visual activation sites were identified by retinotopic mapping and cortical flattening. In addition, one psychophysical and two fMRI experiments were performed to control for differences in visuospatial attention and motor output. Successive color discrimination involved early visual areas, including V1 and VP and the ventral color-responsive region, as well as anterior and middle dorsal intraparietal sulcus, dorsal premotor cortex and pre-SMA. Cortical regions involved in dimming detection and motor output included area V3A, hMT/V5+, lateral occipital sulcus, posterior dorsal intraparietal sulcus, primary motor cortex and SMA. These experiments demonstrated that even with color as the attribute, successive discrimination, in which a decision process has to link visual signals to motor responses, involves both ventral and dorsal visual stream areas.

Adult↗
PubMed2004

Effects of variability in anatomical reconstruction techniques on models of synaptic integration by dendrites: a comparison of three Internet archives.

The first step in building a realistic computational neuron model is to produce a passive electrical skeleton on to which active conductances can be grafted. For this, anatomically accurate morphological reconstructions of the desired cell type are required. In this study compartmental models were used to compare from a functional perspective three on-line archives of rat hippocampal CA1 pyramidal cell morphologies. The topological organization of cells was found to be similar for all archives, but several morphometric differences were observed. The three-dimensional size of the cells, the diameter and tortuosity of dendrites, and the electrotonic length of the main apical dendrite and of the branches in stratum lacunosum moleculare were dissimilar. The experimentally measured kinetics of somatically recorded inhibitory postsynaptic currents evoked in the stratum lacunosum moleculare (data from the literature) could be reproduced only using the archives that contained cells with an electrotonically short main apical dendrite. In the amplitude attenuation of the simulated postsynaptic currents and the voltage escape from the command potential under voltage clamp conditions, a two- to three-fold difference was observed among archives. Upon activation of a single model synapse on distal branches, cells with low dendritic diameter showed a voltage escape larger than 15 mV. The diameter of the dendrites influenced greatly the results, emphasizing the importance of methods that allow an accurate measurement of this parameter. Our results indicate that there are functionally significant differences in the morphometric data available in different archives even if the cell type, brain region and species are the same.

Archives↗
PubMed2003

Resonant synchronization in heterogeneous networks of inhibitory neurons.

Brain rhythms arise through the synchronization of neurons and their entrainment in a regular firing pattern. In this process, networks of reciprocally connected inhibitory neurons are often involved, but what mechanism determines the oscillation frequency is not completely understood. Analytical studies predict that the emerging frequency band is primarily constrained by the decay rate of the unitary IPSC. We observed a new phenomenon of resonant synchronization in computer-simulated networks of inhibitory neurons in which the synaptic current has a delayed onset, reflecting finite spike propagation and synaptic transmission times. At the resonant level of network excitation, all neurons fire synchronously and rhythmically with a period approximately four times the mean delay of the onset of the inhibitory synaptic current. The amplitude and decay time constant of the synaptic current have relatively minor effects on the emerging frequency band. By varying the axonal delay of the inhibitory connections, networks with a realistic synaptic kinetics can be tuned to frequencies from 40 to >200 Hz. This resonance phenomenon arises in heterogeneous networks with, on average, as few as five connections per neuron. We conclude that the delay of the synaptic current is the primary parameter controlling the oscillation frequency of inhibitory networks and propose that delay-induced synchronization is a mechanism for fast brain rhythms that depend on intact inhibitory synaptic transmission.

Action Potentials↗
PubMed2003

A higher order motion region in human inferior parietal lobule: evidence from fMRI.

The proposal that motion is processed by multiple mechanisms in the human brain has received little anatomical support so far. Here, we compared higher- and lower-level motion processing in the human brain using functional magnetic resonance imaging. We observed activation of an inferior parietal lobule (IPL) motion region by isoluminant red-green gratings when saliency of one color was increased and by long-range apparent motion at 7 Hz but not 2 Hz. This higher order motion region represents the entire visual field, while traditional motion regions predominantly process contralateral motion. Our results suggest that there are two motion-processing systems in the human brain: a contralateral lower-level luminance-based system, extending from hMT/V5+ into dorsal IPS and STS, and a bilateral higher-level saliency-based system in IPL.

Adult↗
PubMed2003

Neuroscience data and tool sharing: a legal and policy framework for neuroinformatics.

The requirements for neuroinformatics to make a significant impact on neuroscience are not simply technical--the hardware, software, and protocols for collaborative research--they also include the legal and policy frameworks within which projects operate. This is not least because the creation of large collaborative scientific databases amplifies the complicated interactions between proprietary, for-profit R&D and public "open science." In this paper, we draw on experiences from the field of genomics to examine some of the likely consequences of these interactions in neuroscience. Facilitating the widespread sharing of data and tools for neuroscientific research will accelerate the development of neuroinformatics. We propose approaches to overcome the cultural and legal barriers that have slowed these developments to date. We also draw on legal strategies employed by the Free Software community, in suggesting frameworks neuroinformatics might adopt to reinforce the role of public-science databases, and propose a mechanism for identifying and allowing "open science" uses for data whilst still permitting flexible licensing for secondary commercial research.

Computational Biology↗
PubMed2003

Involvement of multiple functionally distinct cerebellar regions in visual discrimination: a human functional imaging study.

We investigated the contribution of the human cerebellum to cerebral function during visual discrimination using PET and fMRI. The cognitive task was a successive discrimination of shades of brown with a parametric variation of the stimulus presentation rate and a constant task difficulty. The successive color discrimination task was contrasted to a dimming detection control task, with identical retinal input but with double the number of motor responses. Three sets of activated cerebellar and cerebral regions were observed: rate-dependent and rate-independent color discrimination networks and a motor-and-detection network. The rate-dependent color discrimination network included both an anterior and a posterior activation site in lobule-VI of the two lateral cerebellar hemispheres, whereas the rate-independent network involved a bilateral activation site in lateral Crus-I. Cerebellar sites of the motor-and-detection network were located in medial lobule-V bilaterally, in the vermis, and in posterior left Crus-I and right Crus-II. An additional fMRI study was performed to control for differences in motor output and response timing between the tasks. In this control study, the cerebellar activation sites of the rate-dependent and rate-independent color discrimination networks remained unaltered. The motor-and-detection network included cerebellar activations in posterior left Crus-I and right Crus-II, but none in lobule-V or the vermis. Thus, cerebellar activation sites of the motor-and-detection network could be subdivided into those related to a motor network and those belonging to a dimming detection network. We conclude that successive color discrimination activates multiple, functionally distinct cerebellar regions.

Adult↗